TY - JOUR
T1 - Lack of association of novel mutation Asp397Gly in aftB gene with ethambutol resistance in clinical isolates of Mycobacterium tuberculosis
AU - Giri, Astha
AU - Safi, Hassan
AU - Cabibbe, Andrea Maurizio
AU - Gupta, Shraddha
AU - Narang, Anshika
AU - Tyagi, Gaurav
AU - Shrivastava, Kamal
AU - Kumar, Chanchal
AU - Kumar Sharma, Naresh
AU - Lingaraju, Subramanya
AU - Trovato, Alberto
AU - Battaglia, Simone
AU - Cirillo, Daniela Maria
AU - Bose, Mridula
AU - Alland, David
AU - Varma-Basil, Mandira
N1 - Funding Information:
This work was supported by the Indian Council of Medical Research, India (ICMR) (No. 5/8/5/14/2013-ECD1). AG and KS are supported by fellowship from the Department of Science and Technology, Govt. of India (DST/INT/AUS/GCP-13(C)).We are thankful to Prof. VK Nandicoori, National Institute of Immunology, Delhi, for gifting the shuttle vector pST-K. We are also thankful to Prof. Anuradha Chowdhary, Mycology division, VPCI for the use of Applied Biosystems 3130 Genetic Analyzer. We also wish to acknowledge Anupam Prakash and Ashutosh, Mycology division, VPCI, for their guidance during sequencing procedures.
Funding Information:
This work was supported by the Indian Council of Medical Research, India (ICMR) (No. 5/8/5/14/2013-ECD1 ). AG and KS are supported by fellowship from the Department of Science and Technology, Govt. of India ( DST/INT/AUS/GCP-13(C) ).
Publisher Copyright:
© 2019 Elsevier Ltd
PY - 2019/3
Y1 - 2019/3
N2 - To discover additional genotypic indicators for ethambutol (EMB) resistant M. tuberculosis, we studied polymorphisms in arabinofuranosyl transferase encoding genes aftA (Rv3792), aftB (Rv3805) and aftC (Rv2673) in 38 EMB resistant and 34 EMB susceptible isolates from India and a repository established by the World Health Organization (WHO) Special Programme for Research and Training in Tropical Disease (TDR) by DNA sequencing. The results were correlated with the minimum inhibitory concentration (MIC) of EMB and mutations in embB (Rv3795). The most common non-synonymous polymorphism identified in aftB was Asp397Gly in 12/38 (31.6%) EMB resistant and 3/34 (8.8%) EMB susceptible isolates. Interestingly, 10/12 (83.3%) EMB resistant isolates with aftB Asp397Gly mutation also carried embB306, embB402 or embB497 mutations. Association of Asp397Gly polymorphism with EMB resistance was statistically significant (p 0.0216). However, overexpression of the mutant aftB in M. tuberculosis H37Rv did not exhibit any change in the MIC. Whole genome sequencing of a panel of Indian isolates and SNP cluster grouping (SCG) of TDR strains revealed an association between aftB mutation Asp397Gly and Beijing genotype or SCG2, a cluster group representing the Beijing genotype. To conclude, though aftBAsp397Gly mutation is not associated with EMB resistance, this mutation may be a phylogenetic marker for the Beijing clade.
AB - To discover additional genotypic indicators for ethambutol (EMB) resistant M. tuberculosis, we studied polymorphisms in arabinofuranosyl transferase encoding genes aftA (Rv3792), aftB (Rv3805) and aftC (Rv2673) in 38 EMB resistant and 34 EMB susceptible isolates from India and a repository established by the World Health Organization (WHO) Special Programme for Research and Training in Tropical Disease (TDR) by DNA sequencing. The results were correlated with the minimum inhibitory concentration (MIC) of EMB and mutations in embB (Rv3795). The most common non-synonymous polymorphism identified in aftB was Asp397Gly in 12/38 (31.6%) EMB resistant and 3/34 (8.8%) EMB susceptible isolates. Interestingly, 10/12 (83.3%) EMB resistant isolates with aftB Asp397Gly mutation also carried embB306, embB402 or embB497 mutations. Association of Asp397Gly polymorphism with EMB resistance was statistically significant (p 0.0216). However, overexpression of the mutant aftB in M. tuberculosis H37Rv did not exhibit any change in the MIC. Whole genome sequencing of a panel of Indian isolates and SNP cluster grouping (SCG) of TDR strains revealed an association between aftB mutation Asp397Gly and Beijing genotype or SCG2, a cluster group representing the Beijing genotype. To conclude, though aftBAsp397Gly mutation is not associated with EMB resistance, this mutation may be a phylogenetic marker for the Beijing clade.
KW - Beijing
KW - Ethambutol resistance
KW - Mycobacterium tuberculosis
KW - SNPs
KW - aftB
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U2 - 10.1016/j.tube.2019.01.004
DO - 10.1016/j.tube.2019.01.004
M3 - Article
C2 - 30948176
AN - SCOPUS:85060890921
SN - 1472-9792
VL - 115
SP - 49
EP - 55
JO - Tuberculosis
JF - Tuberculosis
ER -